Review Article: Genetics of Alzheimer Disease

Abstract

Alzheimer disease (AD) is the most common causes of neurodegenerative disorder in the elderly individuals. Clinically, patients initially present with short-term memory loss, subsequently followed by executive dysfunction, confusion, agitation, and behavioral disturbances. Three causative genes have been associated with autosomal dominant familial AD (APP, PSEN1, and PSEN2) and 1 genetic risk factor (APOEε4 allele). Identification of these genes has led to a number of animal models that have been useful to study the pathogenesis underlying AD. In this article, we provide an overview of the clinical and genetic features of AD.

Alzheimer's Disease: Approaches to Pathogenesis in the Genomic Age

“…APP mutations themselves are very rare and it is the PSEN1 gene (encoding presenilin 1) where the majority of AD mutations have been detected (Sherrington, 1995 #674). Mutations in the PSEN2 gene were also found in 1995 (Levy-Lahad et al, 1995) but these are also relatively uncommon (Bekris et al, 2010). In comparison to PSEN1 mutation carriers the PSEN 2 cases had a more variable phenotype, a later onset of disease and a reduced penetrance, but the ratio of A 1-42 :A 1-40 is increased in all monogenic AD brains.…”

Neuroprotection in Perimenopausal Women

“…The rise of microglia-specific genes in aging females is interrelated to a significant decrease in the activation of two pro-neurogenesis pathways evident in aging hippocampus: Notch1 and Presenilin 1 and 2 (PSEN1 and PSEN2) regulated genes [51]: Notch1 is necessary for neural stem cell maintenance [52], the PSEN1 expression regulates neuroprogenitor cell differentiation [53], and the defects in PSEN1 expression are associated with the manifestation of AD in old age [54]. Another change of neuroinflammatory genes in aging women is that of Tyrobp known as TREM2, as a causal regulator in microglia-associated changes in AD [55], and its proper mechanism in AD etiology is still being determined [56].…”

MicroRNA-139 modulates Alzheimer’s-associated pathogenesis in SAMP8 mice by targeting cannabinoid receptor type 2

“…AD is characterized by the loss of intellectual and social skills along with impairment of other cognitive functions. Continuous progressive cell death occurs over the course of the disease (Bekris et al, 2010). Due to the increasing number of elderly individuals in the population, it is expected that the number of people who are living with AD worldwide will increase to 114 million by 2050 (Querfurth and LaFerla, 2010).…”